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Press Release

Data from studies of KALYDECO™ (ivacaftor) showed improvements in lung function in people with cystic fibrosis (CF) who have a specific genetic mutation (G551D)

Vertex Pharmaceuticals
Posted on: 04 Sep 12

- Data presented at the European Respiratory Society congress underscore Vertex’s commitment to changing CF treatment by targeting the underlying cause of the disease -

VIENNA - September 3, 2012 – Vertex Pharmaceuticals Incorporated today presented results from the KALYDECO™ (ivacaftor) clinical trials programme at the European Respiratory Society (ERS) congress in Vienna. Data from three phase 3 studies (STRIVE, ENVISION and PERSIST) show that, in people with CF ages 6 years and older who have at least one copy of the G551D genetic mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, treatment with ivacaftor was associated with a rapid and sustained improvement in lung function (forced expiratory volume in one second, FEV1) and respiratory symptoms.

“Cystic Fibrosis is a life-threatening, inherited disease that can lead to persistent infection and permanent lung damage,” said Stuart Elborn, M.D., ivacaftor investigator and President of the European Cystic Fibrosis Society. “Ivacaftor is the first medicine to treat the underlying cause of cystic fibrosis in people with the G551D mutation, a defect in the CFTR protein. These data showing the consistent and sustained benefit of this medicine confirm that it has the potential to make a significant difference to the lives of children, adolescents and adults with this form of cystic fibrosis.” CF is a rare, genetic disease caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. The CFTR protein works like a channel, regulating the flow of salt and water into and out of cells in a number of organs, including the lungs. A healthy balance helps protect the lungs by creating a thin, watery layer of mucus. When the proteins don’t work properly or don’t exist, abnormally thick, sticky mucus accumulates and can cause chronic lung infections and progressive lung damage. In people with CF with the G551D mutation, ivacaftor helps the defective CFTR protein function more normally.

An estimated 1,100 people in Europe with CF have at least one copy of the G551D mutation. Ivacaftor was licensed by the European Commission on 27 July 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene. Vertex is working closely with national reimbursement authorities in Europe to help make ivacaftor available to eligible people as quickly as possible.

Effects of the CFTR potentiator, ivacaftor, in two phase 3 trials in subjects with CF who have the G551D-CFTR mutation (ERS Abstract 1840, Session 228, Monday @ 10:45 CET)

Analysis of the primary endpoint, absolute change in lung function through 24 weeks of treatment, in the STRIVE and ENVISION 48-week studies shows that 150mg ivacaftor given every 12 hours, in addition to previously prescribed treatments, is associated with a rapid and significant improvement (P<0.0001) compared to previously prescribed treatments given with placebo. In STRIVE, people taking ivacaftor experienced a 55 percent reduction in the risk of pulmonary exacerbations through Week 48 compared to those in the placebo group. In ENVISION, too few people experienced pulmonary exacerbations to make a meaningful comparison between the groups. Pulmonary exacerbations are generally considered periods of worsening in the signs and symptoms of CF that often require treatment with antibiotics and hospital visits.

Fewer people in the ivacaftor treatment groups discontinued treatment due to adverse events than in the placebo groups. The majority of the adverse events associated with ivacaftor were mild to moderate. Adverse reactions very commonly observed in those taking ivacaftor (=1/10) included headache; upper respiratory tract infection (common cold) including sore throat and nasal congestion; rash; diarrhoea; and abdominal pain (stomach ache). One patient in the group receiving ivacaftor reported a serious adverse reaction of abdominal pain.

Long-term safety and efficacy of ivacaftor in subjects with cystic fibrosis who have the G551D-CFTR mutation (ERS abstract 1842, Session 228, Monday @ 11:15 CET)

Data from the long-term, follow-up PERSIST study show that the improvements in lung function among people treated with ivacaftor in the STRIVE or ENVISION studies were sustained for up to a total of 96 weeks of treatment.At the time of this analysis of PERSIST study data, 74 adults and adolescents (ages 12 or older) who were first treated with ivacaftor in the STRIVE study continued treatment in PERSIST and have completed a total of 96 weeks of treatment with ivacaftor. A 9.5 percentage-point mean absolute improvement from the STRIVE baseline in lung function was observed at Week 96. All (26/26) of the children (ages 6 to 11) who were first treated with ivacaftor in the ENVISION study continued treatment in PERSIST and have completed a total of 72 weeks of treatment with ivacaftor. A 10.1 percentage-point mean absolute improvement from the ENVISION baseline in lung function was observed at Week 72.

In addition, the analysis showed that people who switched to ivacaftor after receiving 48 weeks of treatment with placebo in the Phase 3 studies experienced improvements in lung function comparable to those seen in people who received ivacaftor from the beginning of the Phase 3 studies.

Adverse events seen in people receiving ivacaftor in the PERSIST study were generally consistent with those seen with ivacaftor treatment during the original Phase 3 studies. The majority of adverse events associated with ivacaftor were mild or moderate in severity and resolved during the reporting period. No new adverse events were identified.

STRIVE, ENVISION and PERSIST study populations

The STRIVE, ENVISION and PERSIST studies enrolled people with cystic fibrosis who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. STRIVE recruited 161 adolescents and adults with CF who were =12 years of age and had a percent predicted FEV1 at screening of 40 to 90 percent and ENVISION enrolled 52 children with CF ages 6 to 11 years who had a percent predicted FEV1 at screening of 40 to 105 percent. The PERSIST extension study enrolled patients who completed treatment in the phase 3 STRIVE or ENVISION studies (ivacaftor and placebo treatment groups) and met certain other eligibility criteria.

Effect of ivacaftor on lung clearance index and FEV1 in subjects with CF who have the G551D-CFTR mutation and mild lung disease (ERS abstract 1841, Session 228, Monday @ 11.00)

CF-related lung disease is known to start before it’s detectable by deterioration in lung function (FEV1). Once FEV1 has fallen below normal, (80 percent to 85 percent predicted), structural damage may have already occurred; much of this can be irreversible.

Data from a Phase 2 randomized, double-blind, crossover study of people with early-stage CF (FEV1 greater than 90 percent predicted) ages 6 and older who have at least one copy of the G551D mutation were also presented at the congress. These showed that ivacaftor led to statistically significant improvements in lung function, measured by FEV1. Through 29 days of treatment, the mean absolute improvement in lung function was 8.7 percentage points for patients receiving ivacaftor compared to those receiving placebo (P=0.01). These results demonstrate that patients with early stage CF may benefit from ivacaftor.

Vertex continues to pursue goal of treating more people with CF

Vertex is committed to developing new medicines to treat the underlying cause of CF. The company recently initiated two Phase 3 trials for people with CF who have certain CFTR gene mutations that were not evaluated in previous Phase 3 studies. The first study will enroll people 6 years of age and older who have at least one R117H mutation, and a second study will enroll people 6 years of age and older with at least one non-G551D CFTR gating mutation. A third Phase 3 study will be initiated later this year for children with CF aged 2 to 5 years who have at least one gating mutation. Vertex is also conducting two Phase 2 studies of ivacaftor in combination with a CFTR corrector, VX-809 or VX-661, to treat people with the most common form of CF.

Ivacaftor, VX-809 and VX-661 were discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

About Cystic Fibrosis

Cystic fibrosis is caused by defective cystic fibrosis transmembrane conductance regulator (CFTR) proteins that result from mutations in the CFTR gene.

Approximately 70,000 people worldwide have CF, including 35,000 people in Europe.

Today, the median predicted age of survival for a person with CF in Europe is approximately 40 years but the median age of death remains in the mid-20s. There are more than 1,800 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The absence of working CFTR proteins results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. This leads to the build-up of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage.

In some people with CF, CFTR proteins are present at the cell surface but do not work properly (also called a “gating” dysfunction of CFTR). The most common type of “gating” dysfunction is known as the G551D mutation.

About ivacaftor

Ivacaftor was approved by the U.S. Food and Drug Administration in January 2012 and by the European Commission in July 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.

Vertex retains worldwide rights to develop and commercialize ivacaftor. Ivacaftor is under Priority Review by the Therapeutic Product Directorate (TPD) of Health Canada, and an application for review has been submitted to the Therapeutic Goods Administration (TGA) of Australia.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO (ivacaftor)

KALYDECO (150mg tablets) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene.

KALYDECO is not for use in people with CF due to other mutations in the CFTR gene. It is not effective in CF patients with two copies of the F508del mutation (F508del/F508del) in the CFTR gene.

High liver enzymes (transaminases, ALT and AST) have been reported in patients receiving KALYDECO. It is recommended that ALT and AST be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal. Following resolution of transaminase elevations, consider the benefits and risks of resuming KALYDECO dosing. Moderate transaminase elevations are common in subjects with CF. Overall, the incidence and clinical features of transaminase elevations in clinical trials was similar between subjects in the KALYDECO and placebo treatment groups. In the subset of patients with a medical history of elevated transaminases, increased ALT or AST have been reported more frequently in patients receiving KALYDECO compared to placebo.

Use of KALYDECO with medicines that are strong CYP3A inducers such as the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's Wort substantially decreases exposure of KALYDECO which may diminish effectiveness. Therefore, co-administration is not recommended.

The dose of KALYDECO must be adjusted when concomitantly used with potent and moderate CYP3A inhibitors.

KALYDECO can cause serious adverse reactions including abdominal pain and high liver enzymes in the blood. The most common side effects associated with KALYDECO include headache; upper respiratory tract infection (the common cold), including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; and dizziness. These are not all the possible side effects of KALYDECO. A list of the adverse reactions can be found in the full product labeling for each country where KALYDECO is approved. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full U.S. Prescribing Information for KALYDECO at www.KALYDECO.com and the EU Summary of Product Characteristics for KALYDECO at http://goo.gl/N3Tz4.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

Vertex initiated its CF research program in 1998 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. This collaboration was expanded to support the accelerated discovery and development of Vertex's CFTR modulators.

About the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The CF Foundation is a donor-supported nonprofit organization. For more information, visit www.cff.org.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Editor's Details

Vertex
Vertex
http://www.vrtx.com
mediainfo@vrtx.com

Last updated on: 04/09/2012

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